Evidence for/Against Administration of Antifibrinolytic Agents During an Obstetrical Hemorrhage

  • Kerry L. O’BrienEmail author


Antifibrinolytics are lysine analogs that inhibit fibrinolysis by binding to plasminogen and preventing it from binding to a fibrin clot where it can be activated to plasmin. These drugs also bind directly to plasmin and displace it from the fibrin clot. Epsilon aminocaproic acid (amicar) and tranexamic acid (TXA) are FDA approved for the treatment of hemophilia patients for short-term use to reduce or prevent hemorrhage, and to reduce the need for replacement therapy, during and following tooth extraction. They are also approved for the treatment of cyclic heavy menstrual bleeding. This class of drug has been increasingly used to decrease blood loss associated with cardiopulmonary bypass surgery, trauma, hip, knee and spinal surgeries, and to treat thrombocytopenic patients with alloimmune refractoriness and bleeding. Several small-scale studies have shown promise in reducing obstetric hemorrhage. Recently a large randomized controlled trial showed that TXA reduces death due to bleeding from post-partum hemorrhage (PPH) with minimal adverse effects, especially if administered within 3 h of delivery. A second prospective randomized controlled trial to determine if TXA reduces the incidence of PPH is in process.


Antifibrinolytic Fibrinolysis Aminocaproic acid Tranexamic acid Obstetric hemorrhage 


  1. 1.
    Clover Pharmaceuticals Corp. Amicar® [package insert]. Marietta, GA: Clover Pharmaceuticals Corp; 2015.Google Scholar
  2. 2.
    Ferring Pharmaceuticals Inc. Lysteda® [package insert]. Parsippany, NJ: Ferring Pharmaceuticals; 2016.Google Scholar
  3. 3.
    Phizer Injectables. Cyklokapron® [package insert]. Pharmacia and Upjohn Company: New York, NY; 2014.Google Scholar
  4. 4.
    McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012;72:588.Google Scholar
  5. 5.
    Brown JR, et al. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation. 2007;115:2801–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Ngaage DL, et al. Lessons from aprotinin: is the routine use and inconsistent dosing of tranexamic acid prudent? Meta-analysis of randomised and large matched observational studies. Eur J Cardiothorac Surg. 2010;37:1375–83.CrossRefPubMedGoogle Scholar
  7. 7.
    CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23–32.CrossRefGoogle Scholar
  8. 8.
    Kagoma YK, et al. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systemic review of randomized trials. Thromb Res. 2009;123:687–96.CrossRefPubMedGoogle Scholar
  9. 9.
    Zufferey P, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105:1034–46.CrossRefPubMedGoogle Scholar
  10. 10.
    Berenholtz SM, et al. Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery. Spine. 2009;34:2096–103.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Elwatidy S, et al. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind placebo controlled study. Spine. 2008;33:2577–80.CrossRefPubMedGoogle Scholar
  12. 12.
    Dzik S. How I do it: platelet support for refractory patients. Transfusion. 2007;47:374–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Bradley LD, Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016;214:31–44.CrossRefPubMedGoogle Scholar
  14. 14.
    Srivaths LV, et al. Oral tranexamic acid versus combined oral contraceptives for adolescent heavy menstrual bleeding: a pilot study. J Pediatr Adolesc Gynecol. 2015;28:254–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Tengborn L, et al. Tranexamic acid—an old drug still going strong and making a revival. Thromb Res. 2015;135:231–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Goshtasebi A, et al. Treatment of heavy menstrual bleeding of endometrial origin: randomized controlled trial of medroxyprogesterone acetate and tranexamic acid. Arch Gynecol Obstet. 2013;288:1055–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Muse K, et al. Long-term evaluation of safety and health-related quality of life in women with heavy menstrual bleeding treated with oral tranexamic acid. Womens Health. 2011;7:699–707.Google Scholar
  18. 18.
    Bonnar J, et al. Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid and tranexamic acid. BMJ. 1996;313:579.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ker K, Shakur H, Roberts I. Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. BJOG. 2016;123:1745–52.CrossRefPubMedGoogle Scholar
  20. 20.
    Ducloy-Boouthors A, et al. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care. 2011;15:R117.CrossRefGoogle Scholar
  21. 21.
    Movafegh A, et al. Effect of tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynecol Obstet. 2011;115:224–6.CrossRefGoogle Scholar
  22. 22.
    Xu J, et al. Tranexamic acid for the prevention of postpartum hemorrhage after cesarean section: a double-blind randomization trial. Arch Gynecol Obstet. 2013;287:463–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Mirghafourvand M, et al. The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: a double-blind randomised controlled trial. Aust N Z J Obstet Gynecol. 2015;55:53–8.CrossRefGoogle Scholar
  24. 24.
    Sentilhes L, et al. Study protocol. TRAAP—RAnexamic acid for preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial. BMC Pregnancy Childbirth. 2015;15:135.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): An international, randomized, double-blind, placebo-controlled trial. Lancet. 2017;389:2105–16.CrossRefGoogle Scholar
  26. 26.
    Roberts I, et al. Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials. 2017;18:48.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ortmann E, et al. Antifibrinolytic agents in current anaesthetic practice. Br J Anaesth. 2013;111(4):549–63.CrossRefPubMedGoogle Scholar
  28. 28.
  29. 29.
    Savage WJ. Transfusion reactions. Hematol Oncol Clin N Am. 2016;30(3):619–34.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Blood BankBeth Israel Deaconess Medical CenterBostonUSA

Personalised recommendations